1. Field of the Invention
The present invention relates generally to cross-linked polymeric compositions and to the use of such compositions for inhibiting tissue adhesion and other purposes.
Tissue adhesions occur frequently following surgery and may contribute to or cause compromised surgical results and post-surgical complications. Tissue adhesions may result from unwanted or excessive scar tissue and occur in various body regions including pelvic, abdominal, spinal, tendon, ophthalmic, urinary, thoracic and cardiovascular tissues and are formed when normal tissue bonds to the surfaces of internal organs which have been traumatized or damaged during surgery. Such adhesions may join organs or other body tissues that normally are separate. Treating adhesions may necessitate additional surgery with additional costs, danger and/or discomfort to the patient.
Of particular pertinence to the present application, tissue adhesions often occur after spinal surgery as the result of scar tissue formation between the spinal cord nerves, and adjacent underlying tissues. Such scar tissue formation can compress the nerve roots, producing neural complications such as persistent low back pain and sciatica. At present, peridural scar tissue must be treated with additional surgery.
Numerous procedures and materials have been proposed to minimize or eliminate post-surgical adhesions. Such procedures include introducing barrier materials such as metals, polymers, and natural materials over the target site. A woven material of regenerated cellulose is currently marketed for this purpose by Johnson & Johnson under the trademark Interceed.RTM.. This product, however, does not conform well to the underlying tissue. Other polymeric materials that have been tried for this purpose include nylon, cellophane, PTFE, polyethylene, siloxane, elastomers and polylactic acid copolymer films. Many of these materials are not biodegradable and therefore, remain in the body with unpredictable and potentially undesirable consequences.
The reduction and elimination of post-surgical spinal adhesions has been particularly problematic. A variety of permanently implanted devices have been proposed, such as those described in U.S. Pat. Nos. 5,437,672 and 4,013,078. The use of permanent implants, however, is undesirable. The use of resorbable barriers and films has also been proposed. Placement of such barriers and films, however, has also been problematic. The regions between adjacent vertebrae are difficult to access, and it is very difficult to properly place and immobilize barriers and films. The use of non-solid anti-adhesive materials is also problematic since such materials must be sufficiently fluid to enter and conform to the regions being treated, while being sufficiently viscous and persistent so that they remain in the space until the tissue is healed. These objectives must further be balanced with the requirements of biocompatibility and resorbability of the anti-adhesive compositions.
For these reasons, it would be desirable to provide improved compositions, methods, and articles for inhibiting the formation of tissue adhesions following surgery and other trauma. In particular, it would be desirable to provide compositions and methods for introducing such compositions in vivo for the prevention and inhibition of peridural adhesions following laminectomies or other surgical procedures on the spinal column. It would be further desirable if such compositions were useful for the prevention or inhibition of adhesions elsewhere in the body and for other in vivo purposes, such as a filler for tissue voids such as divots resulting from tissue biopsies or other blunt tissue trauma, the filling of implants, such as breast implants, the sealing and/or hemostasis of percutaneous penetrations, and the filling and supplementation of other constrained regions within a patient's body. Moreover, the compositions and methods of the present invention should be adaptable for delivering drugs and other biologically active substances to tissue surfaces adjacent to regions where the compositions have been implanted. At least some of these objectives will be met by the embodiments of the invention of the present application described hereinafter.
2. Description of the Background Art
Barrier films and materials used for preventing or inhibiting spinal and other adhesions are described in U.S. Pat. Nos. 5,350,573, 5,140,016; 5,135,751; 5,134,229; 5,126,141;, 5,080,893; 5,017,229; 5,007,916; PCT publications WO 92/21354; WO 95/15747; WO 86/00912; and Boyers et al. (1988) Fert. Ster. 49: 1066-1070. U.S. Pat. Nos. 5,437,672 and 4,013,078 each describe intervertebral protective devices which remain as permanent implants along the patient's spinal cord.
Collagen and other polymeric plugs intended for sealing percutaneous penetrations, such as tissue tracts created by accessing the femoral artery, are described in a number of patents, including U.S. Pat. Nos. 5,540,715, 5,531,759, 5,478,352; 5,275,616; 5,192,300; 5,108,421; and 5,061,274.
Collagen-containing compositions which have been mechanically disrupted to alter their physical properties are described in U.S. Pat. Nos. 5,428,024; 5,352,715; and 5,204,382. These patents generally relate to fibrillar and insoluble collagens. An injectable collagen composition is described in U.S. Pat. No. 4,803,075. An injectable bone/cartilage composition is described in U.S. Pat. No. 5,516,532. A collagen-based delivery matrix comprising dry particles in the size range from 5 .mu.m to 850 .mu.m which may be suspended in water and which has a particular surface charge density is described in WO 96/39159. A collagen preparation having a particle size from 1 .mu.m to 50 .mu.m useful as an aerosol spray to form a wound dressing is described in U.S. Pat. No. 5,196,185.
A polymeric, non-erodible hydrogel that may be cross-linked and injected via a syringe is described in WO 96/06883. A polyoxyalkylene polymer for inhibiting adhesion is described in U.S. Pat. No. 5,126,141.
The following pending applications, assigned to the assignee of the present application, contain related subject matter: U.S. Ser. No. 60/050,437, filed on Jun. 18, 1997; U.S. Ser. No. 08/704,852, filed on Aug. 27, 1996; U.S. Ser. No. 08/673,710, filed Jun. 19, 1996; U.S. Ser. No. 60/011,898, filed Feb. 20, 1996; U.S. Ser. No. 60/006,321, filed on Nov. 7, 1996; U.S. Ser. No. 60/006,322, filed on Nov. 7, 1996; U.S. Ser. No. 60/006,324, filed on Nov. 7, 1996; and U.S. Ser. No. 08/481,712, filed on Jun. 7, 1995. The full disclosures of each of these applications is incorporated herein by reference.